This research program aims to develop new and efficient methods for the preparation of complex bioactive organic molecules. Research proposed in the K99 Mentored phase will be carried out over 1-2 years with Professor Larry Overman and involve the discovery of new asymmetric Pd(ll)-catalyzed reactions of allylic trichloroacetimidates. Pending the development of this methodology, it will be evaluated in the context of an efficient synthesis of microphyllaquinone, a small molecule that exhibits cytotoxicity against several cell lines. The ROO Independent phase (years 3-5) will focus on the discovery of an asymmetric metal-mediated coupling reaction to promote the formation of all-carbon quaternary stereocenters, a challenge often encountered in complex molecule synthesis. This powerful methodology will be expanded to include cascade reactions for the rapid construction of enantioenriched fused and bicyclic ring systems beginning from simple, prochiral starting materials. Finally, the asymmetric total syntheses of two potent antiinflammatory compounds, mangicols A and C, will be pursued. If the goals of this proposal are achieved, new chemical methods for preparing biologically active molecules will be developed. Ultimately, this contribution will facilitate the discovery of new medicinal agents for treating human illnesses.